Leu-enkephalin, tamoxifen and ethanol interactions: effects on motility and hepatic ethanol metabolizing enzymes.
1. Short-term treatment with tamoxifen (a nonsteroidal antiestrogen) decreased mouse spontaneous locomotor activity compared to controls. 2. Short-term pretreatment with tamoxifen prior to an acute sedative dose of ethanol potentiated ethanol-medicated behavioral depression in the mouse. 3. Injection of a small dose of Leu-enkephalin, which is devoid of effect on mouse motility, prior to an acute sedative dose of ethanol to tamoxifen pretreated female mice counteracted ethanol-produced suppression of motor activity. 4. Mouse liver aldehyde dehydrogenase was inhibited by the short-term administration of tamoxifen when given alone or preceding acute dosages of Leu-enkephalin. Concomitantly, there was an increase in blood plasma ethanol concentration from corresponding control. 5. The results of the behavioral performance test used suggest that tamoxifen possesses depressant property and exerts synergestic effect with Leu-enkephalin in antagonizing ethanol-produced behavioral depression in the mouse. 6. The enzymatic part of the study indicates an adverse metabolic influence by tamoxifen on hepatic metabolism of ethanol-derived acetaldehyde which could contribute to the potentiation of the sedative effect of ethanol.
Messiha
F S
FS
Texas Tech University Health Sciences Center, School of Medicine, Lubbock.
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D004347:Drug Interactions; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology*
D013629:Tamoxifen; D000431:Ethanol; D004743:Enkephalin, Leucine; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase